US8460705B2ExpiredUtilityA1

Threo-DOPS controlled release formulation

77
Assignee: PEROUTKA STEPHENPriority: May 12, 2003Filed: Mar 13, 2012Granted: Jun 11, 2013
Est. expiryMay 12, 2023(expired)· nominal 20-yr term from priority
Inventors:Stephen PeroutkaJames Swarbrick
A61K 9/0002A61K 9/1652A61K 9/2077A61K 9/1623A61K 9/1611A61P 25/00A61K 9/4866A61K 9/2866A61K 9/1635A61K 9/2054A61P 29/00A61K 31/198
77
PatentIndex Score
2
Cited by
127
References
44
Claims

Abstract

The present invention relates to pharmaceutical formulations for the controlled delivery of threo-3-(3,4-dihydroxyphenyl)serine (threo-DOPS) and derivatives of it. Such formulations can contain an extended or slow release component that maintains therapeutic concentration of threo-DOPS in the blood plasma over a prolonged time period. They can be further combined with an immediate release formulation to produce a product that, when administered to a patient in need thereof, results in substantially steady levels of active drug, eliminating the sharp peaks and troughs in blood plasma drug levels experienced with the existing threo-DOPS formulations.

Claims

exact text as granted — not AI-modified
The invention claimed is: 
     
       1. A pharmaceutical formulation, comprising: 45-85% by weight of threo-3-(3,4-dihydroxyphenyl)serine, a derivative thereof, or a pharmaceutically-acceptable salt thereof, in an extended release form adapted for release over a period of time of at least 6 hours by dissolution controlled release, diffusion controlled release, or dissolution and diffusion controlled release; and 15-55% by weight of threo-3-(3,4-dihydroxyphenyl)serine, a derivative thereof, or a pharmaceutically-acceptable salt thereof, in an immediate release form; wherein the formulation is adapted for oral delivery. 
     
     
       2. The pharmaceutical formulation of  claim 1 , wherein the pharmaceutical formulation comprises a slowly soluble material which is selected from the group consisting of: ethylcellulose, cellulose acetate phthalate, acrylic resins, methacrylate hydrogels, methylmethacrylate, polymethacrylate, polylactic acid, polyvinyl chloride, hydroxypropylmethylcellulose, polyethylene glycols, carboxymethylcellulose, and sodium carboxymethylcellulose. 
     
     
       3. The pharmaceutical formulation of  claim 1 , wherein the pharmaceutical formulation is suitable for once-daily administration. 
     
     
       4. The pharmaceutical formulation of  claim 1 , wherein the pharmaceutical formulation is suitable for twice- or three-times daily administration. 
     
     
       5. The pharmaceutical formulation of  claim 1 , wherein the extended release form comprises an excipient selected from the group consisting of lubricants, channeling agents, surfactants, fillers, and combinations thereof. 
     
     
       6. The pharmaceutical formulation of  claim 1 , wherein the extended release form comprises an excipient selected from the group consisting of silicon dioxide, magnesium stearate, sodium lauryl sulfate, sodium taurocholate, polysorbate, lactose, hydroxypropylmethylcellulose, ethylcellulose, triethyl citrate, microcrystalline cellulose, polyvinyl alcohol, sodium chloride, dibasic calcium phosphate, polyvinylpyrrolidone, and mixtures thereof. 
     
     
       7. The pharmaceutical formulation of  claim 1 , wherein the threo-3-(3,4-dihydroxyphenyl)serine, a derivative thereof, or a pharmaceutically-acceptable salt thereof, in an extended release form is provided in particulate form. 
     
     
       8. The pharmaceutical formulation of  claim 7 , wherein the particles are coated with a water-insoluble polymeric membrane coating. 
     
     
       9. The pharmaceutical formulation of  claim 8 , wherein the water-insoluble polymeric membrane coating comprises one or more coating materials selected from the group consisting of shellacs, beeswax, glyceryl monostearate, glyceryl palmostearate, stearyl alcohol, ethylcellulose, cellulose acetate phthalate, acrylic resins, methacrylate hydrogels, methylmethacrylate, polymethacrylate, polylactic acid, polyvinyl chloride, hydroxypropylmethylcellulose, polyethylene glycols, carboxymethylcellulose, sodium carboxymethylcellulose, and mixtures thereof. 
     
     
       10. The pharmaceutical formulation of  claim 1 , wherein the extended release form further comprises an osmotically active salt. 
     
     
       11. The pharmaceutical formulation of  claim 1 , wherein the formulation provides for maximal release of the immediate release form within about 1 to about 3 hours after administration, and provides for maximal release of the extended release form between about 6 to about 24 hours after administration. 
     
     
       12. The pharmaceutical formulation of  claim 1 , wherein one or both of the extended release form and immediate release form of the threo-3-(3,4-dihydroxyphenyl)serine, or a derivative or pharmaceutically-acceptable salt thereof, is released at a rate that is independent of the pH in the gastrointestinal tract. 
     
     
       13. A pharmaceutical formulation comprising: 45-85% by weight of threo-3-(3,4-dihydroxyphenyl)serine, or a derivative or pharmaceutically-acceptable salt thereof, in an extended release form adapted for release over a period of at least 6 hours by continuous diffusion controlled release, wherein the extended release form comprises particles formed of the threo-3-(3,4-dihydroxyphenyl)serine, or a derivative or pharmaceutically-acceptable salt thereof, applied to a surface of non-pareil seeds, and 15-55% by weight of threo-3-(3,4-dihydroxyphenyl)serine, a derivative thereof, or a pharmaceutically-acceptable salt thereof, in an immediate release form, and wherein the formulation is adapted for oral delivery. 
     
     
       14. The pharmaceutical formulation of  claim 13 , wherein the extended release form further comprises an excipient selected from the group consisting of lubricants, channeling agents, surfactants, and fillers. 
     
     
       15. The pharmaceutical formulation of  claim 14 , wherein the excipient is selected from the group consisting of silicon dioxide, magnesium stearate, sodium lauryl sulfate, sodium taurocholate, polysorbate, lactose, hydroxypropylmethylcellulose, ethylcellulose, triethyl citrate, microcrystalline cellulose, polyvinyl alcohol, sodium chloride, dibasic calcium phosphate, polyvinylpyrrolidone, and mixtures thereof. 
     
     
       16. The pharmaceutical formulation of  claim 13 , wherein the particles further comprise a water-insoluble polymeric membrane coating. 
     
     
       17. The pharmaceutical formulation of  claim 16 , wherein the water-insoluble polymeric membrane coating comprises one or more coating materials selected from the group consisting of shellacs, beeswax, glyceryl monostearate, glyceryl palmostearate, stearyl alcohol, ethylcellulose, cellulose acetate phthalate, acrylic resins, methacrylate hydrogels, methylmethacrylate, polymethacrylate, polylactic acid, polyvinyl chloride, hydroxypropylmethylcellulose, polyethylene glycols, carboxymethylcellulose, sodium carboxymethylcellulose, and mixtures thereof. 
     
     
       18. The pharmaceutical formulation of  claim 13 , wherein the particles comprise the non-pareil seeds coated with a composition comprising the threo-3-(3,4-dihydroxyphenyl)serine, or a derivative or pharmaceutically-acceptable salt thereof, a channeling agent, a surfactant, and a filler. 
     
     
       19. The pharmaceutical formulation of  claim 18 , wherein the channeling agent is silicon dioxide, the surfactant is selected from the group consisting of sodium lauryl sulfate, sodium taurocholate, polysorbates, and combinations thereof, and the filler is selected from the group consisting of lactose, sodium chloride, triethyl citrate, and combinations thereof. 
     
     
       20. The pharmaceutical formulation of  claim 13 , wherein the extended release form of the threo-3-(3,4-dihydroxyphenyl)serine, or a derivative or pharmaceutically-acceptable salt thereof, is released at a rate that is independent of the pH in the gastrointestinal tract. 
     
     
       21. The pharmaceutical formulation of  claim 13 , wherein the extended release form further comprises an osmotically active salt. 
     
     
       22. The pharmaceutical formulation of  claim 13 , wherein the formulation provides for maximal release of the immediate release form within about 1 to about 3 hours after administration, and provides for maximal release of the extended release form between about 6 to about 24 hours after administration. 
     
     
       23. The pharmaceutical formulation of  claim 13 , wherein the immediate release form of the threo-3-(3,4-dihydroxyphenyl)serine, or a derivative or pharmaceutically-acceptable salt thereof, is released at a rate that is independent of the pH in the gastrointestinal tract. 
     
     
       24. The pharmaceutical formulation of  claim 13 , wherein the pharmaceutical formulation releases the threo-3-(3,4-dihydroxyphenyl)serine, a derivative thereof, or a pharmaceutically-acceptable salt thereof, at roughly the same rate for a predetermined delivery period of at least about 6 hours. 
     
     
       25. The pharmaceutical formulation of  claim 13 , wherein the formulation is suitable for once daily administration. 
     
     
       26. The pharmaceutical formulation of  claim 13 , wherein the formulation is suitable for twice a day or three times a day administration. 
     
     
       27. A pharmaceutical formulation in an extended release form comprising: 45-85% by weight of threo-3-(3,4-dihydroxyphenyl)serine, or a derivative or pharmaceutically-acceptable salt thereof in an extended release form, 15-55% by weight of threo-3-(3,4-dihydroxyphenyl)serine, a derivative thereof, or a pharmaceutically-acceptable salt thereof, in an immediate release form, a coating/matrix material, a channeling agent, and a filler, wherein the formulation provides continuous release of threo-3-(3,4-dihydroxyphenyl)serine, or a derivative or pharmaceutically-acceptable salt thereof, over a period of at least 6 hours, and wherein the formulation is adapted for oral delivery. 
     
     
       28. The pharmaceutical formulation of  claim 27 , wherein the formulation provides continuous diffusion controlled release of the threo-3-(3,4-dihydroxyphenyl)serine, or a derivative or pharmaceutically-acceptable salt thereof in the extended release form. 
     
     
       29. The pharmaceutical formulation of  claim 28 , wherein the threo-3-(3,4-dihydroxyphenyl)serine, or a derivative or pharmaceutically-acceptable salt thereof, in the extended release form is provided in a core surrounded by a water-insoluble polymeric material. 
     
     
       30. The pharmaceutical formulation of  claim 27 , wherein the formulation provides continuous dissolution controlled release of the threo-3-(3,4-dihydroxyphenyl)serine, or a derivative or pharmaceutically-acceptable salt thereof in the extended release form. 
     
     
       31. The pharmaceutical formulation of  claim 27 , wherein the coating/matrix material is selected from the group consisting of shellacs, beeswax, glyceryl monostearate, glyceryl palmostearate, stearyl alcohol, ethylcellulose, cellulose acetate phthalate, acrylic resins, methacrylate hydrogels, methylmethacrylate, polymethacrylate, polylactic acid, polyvinyl chloride, hydroxypropylmethylcellulose, polyethylene glycols, carboxymethylcellulose, sodium carboxymethylcellulose, and mixtures thereof. 
     
     
       32. The pharmaceutical formulation of  claim 27 , wherein the channeling agent comprises silicon dioxide. 
     
     
       33. The pharmaceutical formulation of  claim 27 , wherein the filler is selected from the group consisting of lactose, sodium chloride, triethyl citrate, and combinations thereof. 
     
     
       34. The pharmaceutical formulation of  claim 27 , further comprising a surfactant. 
     
     
       35. The pharmaceutical formulation of  claim 34 , wherein the surfactant is selected from the group consisting of sodium lauryl sulfate, sodium taurocholate, polysorbates, and combinations thereof. 
     
     
       36. The pharmaceutical formulation of  claim 27 , further comprising a lubricant. 
     
     
       37. The pharmaceutical formulation of  claim 36 , wherein the lubricant comprises magnesium stearate. 
     
     
       38. The pharmaceutical formulation of  claim 27 , further comprising a granulating agent. 
     
     
       39. The pharmaceutical formulation of  claim 27 , further comprising one or more components selected from the group consisting of antioxidants, preservatives, dyes, plasticizers, inert carriers, osmotic barriers, and combinations thereof. 
     
     
       40. The pharmaceutical formulation of  claim 27 , wherein the immediate release form of the threo-3-(3,4-dihydroxyphenyl)serine, or a derivative or pharmaceutically-acceptable salt thereof, is released at a rate that is independent of the pH in the gastrointestinal tract. 
     
     
       41. The pharmaceutical formulation of  claim 27 , wherein the extended release form of the threo-3-(3,4-dihydroxyphenyl)serine, or a derivative or pharmaceutically-acceptable salt thereof, is released at a rate that is independent of the pH in the gastrointestinal tract. 
     
     
       42. The pharmaceutical formulation of  claim 27 , wherein the formulation provides for maximal release of the immediate release form within about 1 to about 3 hours after administration, and provides for maximal release of the extended release form between about 6 to about 24 hours after administration. 
     
     
       43. The pharmaceutical formulation of  claim 27 , wherein the formulation is suitable for once daily administration. 
     
     
       44. The pharmaceutical formulation of  claim 27 , wherein the formulation is suitable for twice a day or three times a day administration.

Join the waitlist — get patent alerts

Track US8460705B2 — get alerts on status changes and closely related new filings.

We store only your email — no account needed. See our privacy policy.